The overall aim is to understand the genetic contribution to Panic Disorder (PD) using well-characterized multiplex families, family-based triads and advanced molecular genetic approaches. Our first submission was weakened by the unavailability of the genome scan. A complete genome scan was released to us from CIDR on 12/7/00 including 392,955 genotypes from 1,005 patient samples using 391 microsatellite markers spaced on average every 9cM over all 22 autosomes and both sex chromosomes. Preliminary analyses indicate a number of strong results. In light of the huge amount of undigested data, it is prudent to undertake two years of careful analyses before pursuing additional data collection or a full collaborative study. Since the last resubmission we have completed non parametric and multipoint linkage analyses. In this resubmission we are testing hypotheses generated by the genome scan focusing on four regions and applying innovative approaches to dissecting this complex disease using the genome data. We have added three consultants with expertise on different aspects statistical genetics. We will prepare an integrated family and DNA data set including Dr. Crowe's and our PD families representing 182 multiplex families and 130 triads, the largest PD sample available worldwide, which can subsequently be made available to the scientific community. This proposal represents competitive renewals from investigators who have held individual grants, but have worked together on the genetics of PD for over 10 years. Three previous Columbia grants have been united in a single R01. Panic Disorder accounts for significant morbidity, potential mortality, and increased medical expenditure. While several pharmacological and behavioral treatments are available, none are fully satisfactory. Understanding the etiology of PD will eventually facilitate the development of more effective treatment and preventive intervention.